1. Field of the Invention
The present invention is directed to methods and equipment for the generation of radioisotopes, particularly the generation of short-lived secondary radioisotopes (also referred to as daughter isotopes) from a gaseous precursor compound including a longer-lived radioisotope, and more particularly for the generation of a 68Ga compound from a 68Ge compound.
2. Description of the Related Art
Radioisotopes are widely used in modern medicine, with perhaps as many as one in every three people treated in a hospital benefiting from the use of a radioisotope through laboratory tests, imaging or treatment. One of the most widely used imaging techniques is Positron Emission Tomography (PET) which relies on positrons generated during the beta decay mode of certain isotopes. When these positively charged positrons combine with a negatively charged electron, the particles are annihilated and emit a pair of gamma rays (also referred to as annihilation radiation) having an energy of 511 keV and traveling in opposite directions.
A PET scanner uses a ring of detectors surrounding a patient who has received a dose of a radioisotope that are able to detect the gamma rays generated by the positron annihilation. Relying on the physics of annihilation radiation, the timing of the detection of the paired gamma rays allows the calculation of their point of origin and can be used to generate computer-assisted image reflecting the frequency and location of the annihilation events activity within the patient.
A number of radioisotopes are used in PET imaging including gallium-68, strontium-82, rubidium-82, fluorine-18, oxygen-15, nitrogen-13 and carbon-11. Some of these isotopes can be generated in sufficient quantities using smaller cyclotrons available to the private sector. Radioisotopes used in imaging work best when a significant fraction of the radioisotope dose is associated with the targeted tissue such as the brain, liver, or tumor. Rubidium-82, for example, is widely used in cardiac imaging because it is a chemical analog to potassium and will, therefore, tend to accumulate in muscle tissue. Rubidium-82 administered to a patient will tend to be present in the heart and, as it decays, will generate the gamma rays used to produce a PET image.
The radioisotopes preferred for PET imaging tend to have a relatively short half-life. The half-life of rubidium-82, for example, is only about 76 seconds. While a short half-life ensures that the radioisotope does not persist within a patient's body, it poses a storage problem as is must be produced only shortly before being administered to a patient. To overcome this problem, a range of radioisotope generators has been developed to produce sufficient quantities of the desired radioisotope from longer-lived precursor isotopes almost on demand.
For example, an exemplary rubidium-82 generator utilizes the strontium-82 as the parent isotope to produce rubidium-82 via beta decay. Strontium-82, which can be readily produced using an accelerator, has a half-life of 25.5 days. The strontium-82 can be loaded in the generator as a solution onto a chromatographic column composed of a resin or other suitable material under conditions that will tend retain both the strontium-82 and the rubidium-82 generated as the strontium decays. The rubidium-82 is then selectively eluted from the column while leaving the strontium-82 behind, typically through the use of specific eluents. Because the strontium-82 is continually decaying and producing rubidium-82, the generator can be periodically flushed with an appropriate eluent to obtain the rubidium-82 as needed.
Like strontium, germanium-68 (written alternatively as Ge-68 or 68Ge) has relatively long half-life of 271 days and decays through electron capture to form gallium-68 (written alternatively as Ga-68 or 68Ga). Gallium-68, in turn, has a half life of about 68 minutes and decays primarily by positron emission to form a stable isotope, Zinc-68, making Ga-68 particularly useful for PET imaging applications. An early 68Ge/68Ga generator developed by Gleason in the 1960's utilized an alumina column as the adsorbant from which the Ga-68 was subsequently recovered by eluting the column with a dilute EDTA solution to form a Ga-68 chelate.
A variety of solvent extraction or column-based Ga-68 generators were developed during the 1960's with some versions becoming commercially available during the 1970's and 1980's. The solvent extraction techniques, however, tended to involve a rather complex chemical separation of the desired Ga-68 and tended to be subject to significant breakthrough of Ge-68 in the desired Ga-68 product. In addition, because of a long half-life of the precursor and because Ge-68 is an Auger electron emitter (emitting on the order of 20 low energy electrons per decay), the adsorbants used to retain the Ge-68 within the generators tended to deteriorate rapidly, further increasing the level of Ge-68 breakthrough in the desired Ga-68 product.